Glucocorticoids are steroid hormones, many of which are potent anti-inflammatory agents. Their physiological effects are not limited to their anti-inflammatory properties, however, nor are their effects restricted specifically to inflamed tissue. Protein, lipid and carbohydrate metabolism can be altered adversely and electrolyte balance can be disturbed particularly when large or repeated therapeutic doses of the anti-inflammatory glucocorticoids are administered.
Certain recently developed synthetic glucocorticoids show promise as therapeutic alternatives to the natural anti-inflammatory glucocorticoids such as cortisone, cortisol and corticosterone. The synthetic analogues, which include dexamethasone and betamethasone, exhibit reduced effects on electrolyte balance and tend therefore to elicit fewer adverse side effects. In many instances, they also exhibit greater potency as anti-inflammatory agents relative to their natural counterparts, presumably owing to their reduced binding affinity for the plasma protein known as corticosteroid binding globulin (CBG). It has been reported that natural glucocorticoids become biologically inactivated upon binding with CBG in the circulation whereas many synthetic glucocorticoids do not bind and thus remain active (see Mickelson et al., Biochemistry 1981, 20, 6211-6218 where binding affinities for some natural and synthetic glucocorticoids relative to CBG are tabled). The capacity of synthetic glucocorticoids to escape CBG-binding and thus to remain free and biologically active following administration is presumed to be at least partly responsible for their enhanced anti-inflammatory properties in vivo.
Apart from the numerous physiological effects exerted by glucocorticoids, their use in treating inflammation is further complicated by their ability to affect a broad range of tissues, whether inflamed or healthy. Because so many tissues are responsive to corticosteroids, they are rarely administered systemically unless inflammation is particularly severe or life threatening.